ArticleZhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences2026
[Inhibitory effect of lonafarnib on anaplastic thyroid carcinoma cells and xenograft tumor growth in nude mice].
Article in Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
objectivesTo investigate the inhibitory effect of the farnesyltransferase inhibitor lonafarnib on anaplastic thyroid carcinoma (ATC), and to elucidate the underlying mechanisms.
methodsThe anti-proliferative effect of lonafarnib on ATC cell lines (8505C, CAL62) was assessed using CCK-8 assay. Cell migration and invasion were evaluated by Transwell assay. Apoptosis was detected by flow cytometry. Western blotting was used to measure protein expression levels of Ras, extracellular signal-regulated kinase (ERK), phosphorylated ERK, poly ADP-ribose polymerase (PARP), cleaved PARP, cysteine aspartic acid specific protease-3 (Caspase-3), cleaved Caspase-3, gasdermin E (GSDME), and GSDME N-terminal fragment (GSDME-N). A subcutaneous xenograft model was established in female BALB/c nude mice (4-6 weeks old). 8505C cells (1×10⁶) were injected into the right back of each mouse. When tumor volume reached 100-150 mm³, the mice were randomly divided into three groups (
resultsLonafarnib significantly inhibited the proliferation of ATC cells in a concentration-dependent manner, with superior efficacy compared to cobimetinib and lenvatinib. After treatment with 5, 10, and 20 μmol/L lonafarnib, the numbers of migrated and invaded 8505C and CAL62 cells were markedly reduced, and the apoptosis rates were increased (all
conclusionsLonafarnib effectively suppresses the malignant progression of ATC both in ATC cell lines and in a BALB/c nude mouse xenograft model. The mechanism involves inhibition of Ras farnesylation and the downstream ERK signaling pathway, leading to activation of Caspase-3/PARP-mediated apoptosis and GSDME-mediated pyroptosis.
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